The application of endoscopic excision of the lesion portion of a polyp and early stage cancer (superficial cancer considered to be free from lymph-node metastasis) of alimentary tracts, including the esophagus, stomach, and colon, has been established, due to recent advances in endoscopic techniques. Although endoscopic mucosal resection (EMR) has been applied as a low-invasive surgical technique for persons whom abdominal surgery would be difficult, such as the aged and persons with serious complications, it is now the first-choice therapy for all patients in view of QOL.
EMR, in general, involves marking the lesion portion and its surrounding area, bulging the lesion portion by injecting a hypertonic saline solution into the submucosal layer of the marked region including the lesion portion, snaring and holding the portion to be removed, cutting off the tissue containing the lesion portion with the aid of a high-frequency current, and then collecting the removed tissue for histological examination (non-patent publication 1).
In order to carry out the incision of mucous membrane in EMR safely, the lesion portion must be drawn away from the muscularis propia. To do so, a liquid (referred to as “liquid for bulging the mucous membrane (or topically injectable liquid)” in this specification), such as hypertonic saline solution, is injected into submucosal layer. If the bulge (elevation) of the mucous membrane including the lesion is not sufficient, incision by snaring at a desired position becomes difficult, which may result in the failure of a reliable incision, or alternatively, perforation by incision of muscularis propia beneath the mucous membrane may be occur. Therefore, a liquid to make the mucous membrane bulge and that can retain the desired level of bulge of the mucous membrane until completion of incision is required.
Another major complication in addition to perforation, is bleeding (hemorrhage) during EMR. Accordingly, epinephrine, a vasoconstrictor, is conventionally added to the hypertonic saline solution in order to reduce bleeding volume (non-patent publication 2). However, although this reduces bleeding, some troublesome hemostatic operations cannot be avoided. In addition, when a low-viscosity liquid such as a saline solution is used as a liquid for bulging the mucous membrane, the liquid tends to leak through the needle hole or the first blade incision.
Recently, in order to overcome these problems, glucose or sodium hyaluronate have been added to the liquid for bulging the mucous membrane. It has been reported that the bulge could be prolonged to about 23 minutes on average by the addition of sodium hyaluronate in an animal experiment using porcine esophagus (non-patent publication 3). However in actuality, more than an hour, and sometimes even several hours, is required to complete EMR. Thus, a longer period to maintain the bulge is desired. On the other hand, in endoscopic submucosal dissection (ESD), a major technique used instead of the snaring method, leakage of liquid at the first blade incision is unavoidable. In addition, even if the period to maintain the bulge can be prolonged by the addition of hyalurinic acid, a hemostatic agent such as epinephrine must still also be added in order to prevent bleeding.
Non patent publication 1: Takuya Hayashi, “Rinsyo to Kenkyu”, Vol. 72, No. 5, pages 52-55, 1995.
Non patent publication 2: “Endoscopic Surgery Sekkai/Hakuri EMR”, Tsuneo Koyama, Nihon Medical Center, pages 30-31, 2003.
Non patent publication 3: Massimo Conio et al., Gastrointestinal Endoscopy, Vol. 56, p 513-516 (2002).